An Investigation of Auditory Processes in Parkinson's Disease: Risk Factors and the Potential Utility of Corrective Hearing Treatments.

帕金森病（PD）是仅次于阿尔茨海默病（Alzheimer's Disease）的第二普遍的神经退行性疾病(3)，是一种多方面的运动障碍，目前在英国影响了约13.7万人（4,5）。虽然我们知道帕金森病是由于大脑基底神经节中多巴胺神经元的逐渐丧失而发生的(6)，但我们不知道是什么导致了多巴胺神经元的丧失。随后，PD目前无法治愈(7)。因此，管理和识别与PD相关的潜在危险因素具有特殊的临床重要性。PD和痴呆，特别是路易体痴呆，具有相似的神经病理、脑化学和症状(8)。重要的是，大约80%的PD患者会受到痴呆的影响(9)。听力损失是痴呆的潜在可改变的危险因素，因此即使是轻微的听力损失也会使痴呆的风险增加一倍（10）。鉴于痴呆和帕金森病的相互关系，听力损失可能也是帕金森病的一个潜在的可改变的危险因素。虽然一些研究已经开始承认帕金森氏症和听力损失的相关性，但需要大规模的分析来充分确定听力损失是帕金森氏症的一个危险因素，还是听力损失是帕金森氏症进展过程中感觉加工受损或药物消耗的次要后果。因此，我建议使用UK Biobank对听力损失、PD诊断、帕金森症状严重程度、抗帕金森药物消耗和人口统计学（如种族、性别和国籍）的相关性进行大规模的二次数据分析。该分析将与听觉神经科学（Plack教授；ManCAD, SENSE-Cog, C4AR）、神经退行性变（Crawford教授；C4AR）和感知（Linkenauger博士）领域的知名研究人员合作进行。健康不平等是我们对健康状况的理解和治疗方面的差异。尽管北非和德系犹太人更容易患帕金森病，但少数民族在研究中的代表性严重不足。与ESRC的目标类似，英国帕金森病协会发起了一项旨在解决健康不平等问题的倡议。为配合这些目标，拟议的研究亦会分析人口统计特征（包括种族、国籍和性别）对(a)帕金森病的整体发病率和(b)听力损失与帕金森病的关系的影响。拟议的研究金旨在：(i)与学术界传播研究成果：以前的博士研究成果和新的研究成果将在大型国际会议上和通过同行评议的出版物发表。（ii）产生非学术产出：与Hedley Emsley教授合作，我将组织一个研究研讨会（针对与PD患者一起工作的个人）。我亦会为PD患者举办研究工作坊。除了这些研讨会之外，还将开发一个摘要信息图，并与研讨会/研讨会的与会者、兰开夏郡教学医院NHS基金会信托基金的成员、兰开夏郡神经科学和C4AR分享。（iii）进行大规模二级数据分析，调查听力损失与PD的相关性（使用UK Biobank）。这些探索性分析的结果将构成资金申请的基础。（iv）提高我的研究技能和协作网络：通过完成额外的研究，我将提高我的数据分析技能，并与该领域的专家建立新的合作关系。这些技能和合作将使我在未来进行进一步的研究。(v)开发资金申请：在奖学金期间，我将开发资金申请：ESRC新研究者资助和ESRC二次数据分析计划。这些资助将调查早期和晚期PD患者听力损失的倾向和影响，以及PD患者听力损失治疗的潜在效用

Parkinson's Disease (PD), the second most pervasive neurodegenerative disorder after Alzheimer's Disease (3), is a multifaceted movement disorder, which currently affects ~137,000 people in the UK (4,5). While we know that PD occurs due to the progressive loss of dopamine neurons in the basal ganglia of the brain (6), we do not know what causes the loss of dopamine neurons to occur. Subsequently, PD is currently incurable (7). Therefore, the management, and identification of potential risk factors associated with PD is of particular clinical importance. PD and dementia, particularly dementia with Lewy bodies, share similar neuropathologies, brain chemistry, and symptoms (8). Importantly, approximately 80% of people with PD are affected by dementia (9). Hearing loss is a potentially modifiable risk factor for dementia, such that even mild hearing loss doubles dementia risk (10). Given the interrelatedness of dementia and PD, it may be that hearing loss is also a potentially modifiable risk factor for PD. While some studies have begun to acknowledge the relatedness of PD and hearing loss, large scale analyses are needed to fully determine whether hearing loss is a risk factor of PD or whether hearing loss is a secondary consequence of impaired sensory processing or medication consumption that occurs over the course of PD progression. Therefore, I propose to conduct a large-scale secondary data analysis, using the UK Biobank, of the relatedness of hearing loss, the diagnosis of PD the severity of Parkinsonian symptomology, anti-Parkinsonian medication consumption, and demographics (e.g. race, sex, and nationality). This analysis will be conducted in collaboration with renowned researchers in the fields of auditory neuroscience (Prof. Plack; ManCAD, SENSE-Cog, C4AR), neurodegeneration (Prof. Crawford; C4AR), and perception (Dr Linkenauger). Health inequalities are disparities in our understanding, and treatment, of health conditions. Although, North African and Ashkenazi Jewish individuals are more likely to develop PD, ethnic minorities are grossly underrepresented in research. Akin to the ESRC objectives, Parkinson's UK has launched an initiative that aims to tackle health inequalities. In line with these objectives, the proposed study will also analyse the influence of demographic characteristics including race, nationality and sex, on (a) the overall occurrence of PD and (b) the relatedness of hearing loss and PD.The proposed fellowship aims to:(i) Disseminate findings with academics: Previous PhD findings, and new findings will be presented at large international conferences and through peer-reviewed publications. (ii) Generate non-academic output: In collaboration with Professor Hedley Emsley, I will organise a research symposium (targeted to individuals working with people with PD). I will also organise a research workshop for individuals with PD. In addition to these workshops, a summary infographic will be developed and shared with workshop/symposium attendees, members of Lancashire Teaching Hospitals NHS Foundation Trust, Lancashire Neuroscience, and the C4AR. (iii) Conduct a large-scale secondary data analysis investigating the relatedness of hearing loss and PD (using the UK Biobank). The results of these exploratory analyses will form the basis of funding applications.(iv) Enhance my research skills and collaborative networks: By completing additional research, I will enhance my data analysis skills and develop new collaborations with experts in the field. These skills and collaborations will allow me to conduct further research in the future. (v) Develop funding applications: During the fellowship, I will develop funding applications: The ESRC New Investigator grant, and the ESRC Secondary Data Analysis Initiative. These grants will investigate the propensity and effects of hearing loss in individuals with both early stage and advanced PD, and the potential utility of treatments to correct hearing loss in PD